Image display apparatus, image display method, and image processing method

ABSTRACT

An image display apparatus  120  for imaging and displaying a test substance contained in a sample  111  includes an imaging unit  200  for imaging a test substance, an image processing unit  121  for generating an image  61  for display including an additional image  11   c  in which the pixel value of each pixel is set in uneven distribution added to at least part of the captured image  11  obtained by the imaging unit  200  and a region  21  of the test substance, and a display unit  123  for displaying the image  61  generated by the image processing unit  121.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from Prior Japanese Patent ApplicationNo. 2017-090460, filed on Apr. 28, 2017, entitled “IMAGE DISPLAYAPPARATUS, IMAGE DISPLAY METHOD, AND IMAGE PROCESSING METHOD”, theentire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to an image display apparatus, an imagedisplay method, and an image processing method for imaging anddisplaying a test substance.

BACKGROUND

An apparatus for analyzing a test substance contained in a cell byimaging a cell and processing the captured image is used in facilitiessuch as hospitals. This type of apparatus generally has a configurationfor extracting and displaying an image including a test substance from acaptured image. When examining the result of analysis by the apparatus,the operator can visually confirm the appearance state of the testsubstance by appropriately displaying an image including the testsubstance on a monitor or the like.

Japanese Patent Application Publication No. 07-286952 describes aconfiguration that cuts out an image of particles such as cells from acaptured image to generate a display image. In this configuration,particle images 311 to 314 are displayed in the display areas 301 to 304as shown in FIG. 24. The areas other than the images 311 to 314 of theparticles in the display areas 301 to 304 are filled with white orblack, or are painted out with the average density data of thebackground portions of the particle images 311 to 314.

SUMMARY OF THE INVENTION

The image of the particle cut out from the captured image includes thearea of the particle and the background area. Among these, thebackground area does not become a uniform pixel value due to thecharacteristics of imaging, but becomes a random pixel value includingundulation and a noise component. In the method of the above-mentionedJapanese Patent Application Publication No. 07-286952, the region otherthan the image of the particle is filled with a single color, sovisibility greatly differs between this region and the background regionof the particle image. For this reason, an unnatural image in which aregion other than the particle image is conspicuous is displayed, andwhen the operator visually confirms the image, there is a possibilitythat operating efficiency is lowered.

In view of this problem, the invention provides an image displayapparatus, an image display method, and an image processing methodcapable of displaying an image including a test substance as a morenatural image.

A first aspect of the invention relates to an image display apparatus(120) for imaging and displaying a test substance contained in a sample(111). An image display apparatus (120) according to this aspectincludes an imaging unit (200) for imaging a test substance, aprocessing unit 121 for adding an additional image (11 c) in which thepixel value of each pixel is set so as to be distributed non-uniformlyin at least a part of captured images (11 to 14) obtained by the imagingunit (200) to display images (61 to 64, and 70) for display includingthe regions (21 to 24), and a display unit (123) for displaying theimages for display (61 to 64, and 70) generated by the image processingunit (121).

The sample is a liquid prepared based on blood, plasma, cerebrospinalfluid, interstitial fluid, urine or the like collected from a livingbody. The substance to be tested is a substance derived from a livingbody and is a specific gene in a cell, a specific substance contained inthe nucleus of a cell, a specific substance in a cell membrane, anucleus in a cell, a cell membrane, a cell, a protein or the like. Thepixel value is a digital value assigned to each pixel of the image.

The pixel value of each pixel is generally nonuniform in the regionother than the region of the test substance in a captured image, thatis, in the background region. According to the image display apparatusof this aspect, the pixel value of each pixel of the additional image isset so that the pixel values are unevenly distributed similar to thebackground area of the captured image. In this way it is possible todisplay a natural image in which the additional image is similar to thebackground area of the captured image. Hence, the operator canconcentrate on the region of the test substance without being distractedby the unnatural image, and can visually confirm the display imageefficiently.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to generate a display image (61 to64, and 70) so that the position of the region (21 to 24) of the testsubstance in the captured image (11 to 14) differs from the position ofthe test substance (21 to 24) in the display image (61 to 64, and 70).

In the image display apparatus (120) according to this aspect, thedisplay unit (123) is configured to display a list of a plurality ofdisplay images (61 to 64, and 70) generated from the same sample (111).In this way, the operator can easily compare and contrast images fordisplay based on the same sample.

In this case, the imaging unit (200) images a plurality of testsubstances of the same type, and the image processing unit (121)generates, for each of a plurality of captured images (11) obtained bythe imaging unit (200) based on a plurality of test substances of thesame type, display images (61 to 64, 70) for display so that thepositions of the region (21) of the test substance are the same in thedisplay images (61, 70). In this way, since the regions of the testsubstance are positioned at the same position in the plurality ofdisplay images to be listed, the operator can efficiently proceed withthe visual confirmation of the test substance.

In this case, the image processing unit (121) is configured to generatedisplay images (61 to 64, and 70) by respectively adding mutuallydifferent additional images (11 c) corresponding to the backgroundregion other than the region (21 to 24) of the test substance to atleast part of the plurality of captured images (11 to 14). In this way,a natural image in which the additional image is similar to thebackground region of the captured image is displayed, so that theoperator can concentrate on the region of the test substance without thedistraction of an unnatural image in the visual confirmation.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) may be configured to set the display images (61 to64, 70) to a fixed shape and a fixed size. The display image can be madeeasy to see by matching the shape and size of the display image. Hence,it is possible to increase working efficiency when visually observingthe state of the test substance.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to generate a display image (61 to64, and 70) by adding an additional image (11 c) to at least part of thecaptured image (11 to 14) so that the region (21) of the test substanceis positioned substantially at the center of the display image (61, 70).In this way, since the region of the test substance is positionedsubstantially at the center of the display image, the operator canalways confirm the test substance at substantially the center of thedisplay image so that visual confirmation of the display image proceedsefficiently.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to acquire the average pixel valueof the background region (91, 92) other than the region (21 to 24) ofthe test substance from the captured images, and set the pixel value ofeach pixel of the additional image (11 c) based on the acquired averagepixel value. In this way, the pixel value of the additional image can beset within the range of the pixel values close to the average pixelvalue of the background area. Hence, a differential of the pixel valuebetween the background region of the captured image and the additionalimage can be suppressed, and a natural image in which the additionalimage is similar to the background area of the captured image can bedisplayed.

Note that the background region is not necessarily the entire region ofthe background area excluding the region of the test substance from thecaptured image, and may be a part of the background area. For example,in the case of cutting out a part of a captured image to generate adisplay image, the background area may be the entire region of thebackground area excluding the area of the test substance from the cutoutimage, or the region of part of the background area in the vicinity ofthe boundary with the additional image.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to acquire the average pixel valueof the background region (91, 92) other than the region (21 to 24) ofthe test substance from the captured images, and set the pixel value ofeach pixel of the additional image (11 c) based on the acquired averagepixel value. The “average pixel value similar to the average pixel valueof the background region” is, for example, the average pixel valuestatistically predicted in the background region. In this way, the pixelvalue of the additional image can be set within the range of the pixelvalues close to the average pixel value of the background region. Hence,a differential of pixel values between the background region of thecaptured image and the additional image can be suppressed, and a naturalimage in which the additional image is similar to the background area ofthe captured image can be displayed.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to set the pixel value of each pixelof the additional image (11 c) by changing the pixel value for eachpixel with respect to the average pixel value. In this way, the noisecomponent of the pixel value occurring in the background area can berepresented in the additional image. Therefore, a more natural displayimage can be generated.

In this case, the image processing unit (121) is configured to set thepixel value of each pixel of the additional image (11 c) by adding arandom number of positive or negative polarity for each pixel to theaverage pixel value. In this way, the noise component of the pixel valueoccurring in the background area can be represented in the additionalimage by a simple process.

The image processing unit (121) also is configured to acquire a maximumpixel value and a minimum pixel value of the background region (91, 92),and set the pixel value of each pixel of the additional image (11 c) byadding a random number of either positive or negative polarity to eachpixel relative to the average pixel value so that the pixel value ofeach pixel of the additional image (11 c) is at least between themaximum pixel value and the minimum pixel value. By doing so, the noisecomponent represented in the additional image can be renderedinconspicuous to the background region of the captured image since thepixel value of the additional image falls within the range of pixelvalue change of the background region of the captured image.

The image processing unit (121) also is configured to acquire a maximumpixel value and a minimum pixel value that are similar to the maximumpixel value and the minimum pixel value of the background region (91,92), respectively, and set the pixel value of each pixel of theadditional image (11 c) by adding a random number of positive ornegative polarity to each pixel relative to the average pixel value sothat the pixel value of each pixel of the additional image (11 c) fallsat least between the acquired maximum pixel value and minimum pixelvalue. “Maximum pixel value similar to the maximum pixel value of thebackground region” is, for example, the maximum pixel value that isstatistically predicted in the background region, and “minimum pixelvalue similar to the minimum pixel value of the background region” is,for example, the minimum pixel value statistically predicted in thebackground region. By doing so, the noise component represented in theadditional image can be rendered inconspicuous to the background regionof the captured image since the pixel value of the additional imagefalls within the range of pixel value change similar to the backgroundregion of the captured image.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to acquire pixel values of thebackground region (91, 92) other than the region (21 to 24) of the testsubstance in the captured image (11 to 14), and set the pixel value ofeach pixel of the additional image (11 c) so that the pixel values ofthe additional image (11 c) are distributed with the same tendency asthe frequency distribution of the pixel values of the background region(91, 92) other than the region (21 to 24) of the test substance in thecaptured image (11 to 14). In this way, the noise component can berepresented in the additional image with a pixel value distributionsimilar to the noise component of the background region. Hence, a morenatural display image can be generated.

In this case, the image processing unit (121) is configured to set thepixel value of each pixel of the additional image (11 c) by setting afunction that defines the relationship between the random number and thepixel value based on the frequency distribution of the pixel values ofthe background area (91, 92), and applying a random number in the setfunction. In this way it is possible to smoothly calculate the pixelvalue of each pixel of the additional image.

In this case, the image processing unit (121) acquires the variance ofthe frequency distribution of the pixel values of the background region(91, 92), multiplies the inverse function of the function representingthe Gaussian distribution by the acquired variance, and adds the averagepixel value of the background region (91, 92) to set a function definingthe relationship between the random number and the pixel value.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to set the pixel value of each pixelof the additional image (11 c) by setting the function defining therelationship between the random number and the pixel value based on thesame frequency distribution as the frequency distribution of the pixelvalues of the background regions (91, 92), and applying a random numberto the set function. “Frequency distribution similar to the frequencydistribution of pixel values in the background region” is, for example,a statistically predicted frequency distribution in the pixel value ofthe background region. In this way it is possible to smoothly calculatethe pixel value of each pixel of the additional image.

In this case, the image processing unit (121) acquires the same varianceas the variance of the frequency distribution of the pixel values of thebackground region (91, 92), multiplies the inverse function of thefunction representing the Gaussian distribution by the acquiredvariance, and adds the average pixel value of the background region (91,92) to set a function defining the relationship between the randomnumber and the pixel value. “Variance similar to the variance of thefrequency distribution of pixel values in the background region” is, forexample, statistically predicted variance in the frequency distributionof pixel values in the background region.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) is configured to set the pixel value of each pixelof the additional image (11 c) by acquiring a maximum pixel value and aminimum pixel value of the background image (91, 92) other than theregion (21 to 24) of the test substance in the captured image (11 to 14)based on a random number that varies within the range between theacquired maximum pixel value and the minimum pixel value.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) sets the pixel value of each pixel of theadditional image (11 c) by acquiring a maximum pixel value and minimumpixel value similar to the maximum pixel value and minimum pixel valuein the background area (91, 92) other than the area (21 to 24) of thesubject substance in the captured image (11 to 14), respectively, basedon a random number that varies within the range between the acquiredmaximum pixel value and the minimum pixel value.

In the image display apparatus (120) according to this aspect, the imageprocessing unit (121) executes a smoothing process to suppress pixelvalue change of pixels near the boundary between at least the additionalimage (11 c) and the background areas (91, 92) of the captured image (11to 14). In this way, continuity between the background area of thecaptured image and the additional image is improved, so that a morenatural display image can be generated.

In the image display apparatus (120) according to this aspect, the testsubstance is a substance derived from a living body. By doing so, it ispossible to display an image based on a substance derived from a livingorganism. The operator can smoothly and efficiently advance thediagnosis based on the substance derived from the living body byreferring to the displayed image.

In this case, the test substance is selected from a group including aspecific gene in the cell, a specific substance contained in the nucleusof the cell, a specific substance in the cell membrane, a nucleus in thecell, a cell membrane, a cell, and a protein.

In this case, the test substance contains the BCR gene and the ABL genein the cell. In this way, images based on the BCR gene and the ABL genecan be displayed. Therefore, by referring to the displayed image, forexample, the operator can confirm the translocation of these genes and adiagnosis based on these genes can proceed smoothly and efficiently.

In this case, the image processing unit (121) may be configured tosuperimpose an image (62) based on the BCR gene and an image (63) basedon the ABL gene to generate the display image (70). The operator caneasily confirm the distribution state of the BCR gene and the ABL geneby referring to the image in which the image based on the BCR gene andthe image based on the ABL gene are superimposed. In this way, forexample, it can be easily confirmed whether translocation occurs inthese genes, and diagnosis can smoothly proceed.

In the image display apparatus (120) according to this aspect, the testsubstance includes a specific gene in the cell and a nucleus in thecell, and the image processing unit (121) generates a display image (70)by superimposing a nucleus-based image (61) and a gene based image (62,63). In this way, the operator can ascertain how the gene is distributedin the nucleus. When a gene is labeled with a fluorescent dye, forexample, it can be determined that the fluorescent labeling of the genewas not performed properly if light generated from the fluorescent dyethat labels the gene is distributed outside the nucleus.

In the image display apparatus (120) according to this aspect, the testsubstance is labeled with a fluorescent dye that generates fluorescenceby excitation light, and the imaging unit (200) irradiates the sample(111) containing the test substance with excitation light to capture animage of the fluorescence generated from the fluorescent dye. In thisway, the region, position, and the like of the test substance can bevisualized in the image by the fluorescence. Hence, the operator canconfirm the state of the test substance smoothly and clearly byreferring to the display image.

In this case, the imaging unit (200) includes a flow cell (210) forflowing a sample (111), light sources (221 to 223) for irradiatingexcitation light on the sample (111) flowing through the flow cell, anda camera (254) for imaging the sample (111) irradiated with theexcitation light. In this way, a plurality of captured images based onthe test substance can be continuously acquired from one sample.

A second aspect of the invention relates to an image display apparatus(120) for imaging and displaying a test substance contained in a sample(111). An image display apparatus (120) according to this aspectincludes an imaging unit (200) for imaging a test substance, aprocessing unit (121) for adding an additional image (11 c) in which thepixel value of each pixel is set so as to be distributed non-uniformlyin at least a part of captured images (11 to 14) obtained by the imagingunit (200) to generate display images (61 to 64, and 70) including theregions (21 to 24), and a display unit (123) for displaying the displayimages (61 to 64, and 70) generated by the image processing unit (121).

According to the image display apparatus of this aspect, since the pixelvalue of each pixel of the additional image is set so that the pixelvalues are unevenly distributed similarly to the background area of thecaptured image, a natural image can be generated in which the additionalimage is similar to the background region of the captured image. Then, aplurality of generated images for display are displayed in a list. As aresult, the operator easily concentrates on the region of the testsubstance without being distracted by an unnatural image while easilycomparing and contrasting the display images based on the same sample,and visual confirmation of the display image proceeds efficiently.

A third aspect of the invention relates to an image display apparatus(120) for imaging and displaying a test substance contained in a sample(111). An image display apparatus (120) according to this aspectincludes an imaging section (200) for imaging a test substance, an imageprocessing unit (121) for generating display images (61 to 64, 70)including regions (21 to 24) of the test substance from the capturedimages (11 to 14) obtained by the imaging unit (200), and a display unit(123) for displaying the display images (61 to 64, 70) generated by theimage processing unit (121). The image processing unit (121) generates adisplay image by acquiring a plurality of statistical values relating topixel values of a background region (91, 92) other than the region (21to 24) of the test substance from the captured image (11 to 14), andadding to at least a part of the captured image an additional image (11c) in which the pixel value of each pixel is set so that the pixelvalues are unevenly distributed.

The statistical value is, for example, an average pixel value, a maximumpixel value, a minimum pixel value, a variance of pixel values, and thelike. According to the image display apparatus of this aspect, the sameeffects as those of the first aspect are obtained.

A fourth aspect of the invention relates to an image display method forimaging and displaying a test substance contained in a sample (111). Theimage display method according to this aspect includes a step (S2) ofimaging a test substance, a step (S5) of generating a display image byadding an additional image (11 c) in which the pixel value of each pixelis set so that the pixel values are unevenly distributed on at least apart of the captured image (11 to 14) obtained by imaging and theposition of the region (21 to 24) of the test substance in the capturedimage (11 to 14) and the position of the region (21 to 24) of the testsubstance differ, and a step (S8) of displaying the generated displayimage (61 to 64, and 70).

According to the image display method of this aspect, the same effectsas those of the first aspect are obtained.

A fifth aspect of the invention relates to an image processing methodfor generating a display image (61 to 64, 70) including regions (21 to24) of a test substance from captured images (11 to 14). The imageprocessing method according to this aspect includes a step (S5) ofgenerating a display image (61 to 64, and 70) by adding an additionalimage (11 c) in which the pixel value of each pixel is set so that pixelvalues are distributed unevenly to at least a part of the captured image(11 to 14) so that the position of the region (21 to 24) of the testsubstance in the captured image (11 to 14) differs from the position ofthe region (21 to 24) of the test substance in the display image (61 to64, 70).

According to the image processing method of this aspect, the sameeffects as those of the first aspect are obtained.

According to the invention, it is possible to display a natural image inwhich the additional image is similar to the background region of thecaptured image.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a block diagram showing a configuration of an image displayapparatus and a preprocessing unit according to a first embodiment;FIGS. 1B to 1G are schematic diagrams showing a procedure for generatinga display image from a captured image with respect to the nucleusaccording to the first embodiment;

FIG. 2 is a schematic diagram showing a configuration of an imaging unitaccording to the first embodiment;

FIG. 3 is a flowchart showing processing using a preprocessing unit andan image display apparatus according to the first embodiment;

FIG. 4A is a schematic diagram showing a captured image according to thefirst embodiment; FIG. 4B is a schematic diagram showing a region of atest substance according to the first embodiment; FIG. 4C is a schematicdiagram showing a procedure for acquiring a region of a test substanceaccording to the first embodiment;

FIG. 5A is a schematic diagram showing a region of a display imageaccording to the first embodiment; FIG. 5B is a schematic diagramshowing a deletion area and an additional area according to the firstembodiment; FIG. 5C is a schematic diagram showing a display imageaccording to the first embodiment;

FIG. 6A is a schematic diagram showing that an additional image is addedto a part of the captured image according to the first embodiment; FIG.6B is a schematic diagram showing that an additional image is added tothe entire captured image according to the first embodiment;

FIG. 7A is a schematic diagram showing that a composite display image isgenerated by superimposing display images generated for each testsubstance according to the first embodiment; FIGS. 7B to 7D areschematic diagrams showing cells determined to be positive in detectionof abnormal cells according to the first embodiment;

FIG. 8 is a schematic diagram showing a screen displayed on a displayunit according to the first embodiment;

FIG. 9 is a flowchart showing a padding process according to the firstembodiment;

FIG. 10A is a schematic diagram showing an image in which a deletionimage is removed from a captured image by a clipping processingaccording to the first embodiment; FIG. 10B is a schematic diagramshowing a mask image and a background area according to the firstembodiment; FIG. 10C is a schematic diagram showing a mask image and abackground area according to a modification of the first embodiment;

FIG. 11A is a conceptual diagram describing the pixel value of pixelsset in an additional image according to the first embodiment; FIGS. 11Band 11C are diagrams showing images, mask images, and histogramspost-clipping actually generated according to the first embodiment;

FIG. 12A is a diagram showing a display image actually generated by thepadding process of the first embodiment; FIG. 12B is a diagram showingan image actually generated by the padding process of a comparativeexample;

FIG. 13A is a flowchart showing a modification example of the paddingprocess according to the first embodiment; FIG. 13B is a conceptualdiagram describing the pixel value of pixels set in an additional imageaccording to a modification example of the padding process of the firstembodiment;

FIG. 14A is a flowchart showing a padding process according to a secondembodiment; FIG. 14B is a conceptual diagram describing the pixel valueof the pixels set in an additional image related to the padding processaccording to the second embodiment;

FIG. 15A is a flowchart showing a modification example of the paddingprocess according to the second embodiment; FIG. 15B is a conceptualdiagram describing the pixel value of the pixels set in an additionalimage according to a modification example of the padding process of thesecond embodiment;

FIG. 16A is a flowchart showing a padding process according to a thirdembodiment; FIG. 16B is a schematic diagram showing an applicationregion of the smoothing process according to the third embodiment; FIGS.16C to 16F are schematic diagrams describing the calculation in thesmoothing process according to the third embodiment;

FIG. 17A is a diagram showing a display image actually generated by thepadding process of the third embodiment; FIGS. 17B and 17C are schematicdiagrams describing the calculation in the smoothing process accordingto a modification of the third embodiment;

FIG. 18A is a flowchart showing a padding process according to a fourthembodiment; FIG. 18B is a diagram showing a display image actuallygenerated by the padding process of the fourth embodiment;

FIGS. 19A and 19B are graphs schematically showing the probabilitydensity function according to the fourth embodiment.

FIG. 20A is a graph schematically showing a cumulative distributionfunction according to the fourth embodiment; FIG. 20B is a graphschematically showing the inverse function of the cumulativedistribution function according to the fourth embodiment;

FIG. 21A is a graph schematically showing a probability density functionaccording to the fourth embodiment; FIG. 21B is a schematic diagramdescribing setting the pixel value of each pixel by dividing theadditional area according to the fourth embodiment;

FIG. 22A is a flowchart showing the padding process according to a fifthembodiment; FIG. 22B is a diagram showing a display image actuallygenerated by the padding process of the fifth embodiment;

FIG. 23A is a flowchart showing a padding process according to a sixthembodiment; FIG. 23B is a diagram showing a display image actuallygenerated by the padding process of the sixth embodiment; and

FIG. 24 is a schematic diagram describing a configuration of the relatedart.

DESCRIPTION OF THE EMBODIMENTS OF THE INVENTION

The following embodiments apply the invention to an image displayapparatus in which a test substance contained in a sample is imaged byan imaging unit, an image processing unit generates a display image fromthe captured image obtained by the imaging unit, and the generateddisplay image is displayed on a display unit. The sample is a liquidprepared based on blood collected from the living body. The testsubstance is the target site in the nucleic acid in a cell, the nucleusin the cell, and the cell. The target site in the nucleic acid is theBCR gene on chromosome 22 and the ABL gene on chromosome 9.

The image display apparatus described in the following embodiment alsoanalyzes cells based on captured images. Specifically, cells havingtranslocation between chromosome 9 and chromosome 22 found in chronicmyelogenous leukemia are detected as abnormal cells. That is, in thefollowing embodiment, cells in which the BCR gene or the ABL gene istranslocated to produce the BCR-ABL fusion gene are detected as abnormalcells. In the following embodiment, the cells to be detected are whiteblood cells in a blood sample.

Note that the sample is not limited to a prepared liquid based on blood,and also may be a prepared liquid based on plasma, cerebrospinal fluid,interstitial fluid, urine or the like collected from a living body. Thetest substance also may be any substance derived from a living body, forexample, a substance different from the BCR gene and the ABL gene, aspecific substance contained in the nucleus of the cell, a specificsubstance in the cell membrane, a cell membrane, a protein.

Summary of the First Embodiment

As shown in FIG. 1A, the image display apparatus 120 measures anddisplays a sample 111 prepared by preprocessing performed by apreprocessing unit 110.

The operator performs processing such as centrifugal separation on asample collected from a subject, and extracts leukocytes which are thecells to be detected. The sample is, for example, whole blood ofperipheral blood. In the extraction of white blood cells, leukocytes maybe extracted by hemolyzing other blood cells with a hemolytic agentinstead of centrifugation. The sample containing the extracted whiteblood cells is set in the pretreatment unit 110.

The pretreatment unit 110 includes a mixing container for mixing thereagent and the sample, a dispensing unit for dispensing the sample andreagent to the mixing container, a heating unit for heating the mixingcontainer and the like. The pretreatment unit 110 prepares a sample 111from the placed sample by performing pretreatment that includes a stepof labeling the target site of the cell with a fluorescent dye, and astep of specifically staining the nucleus of the cell with a fluorescentdye for nuclear staining. In the step of labeling the target site withthe fluorescent dye, the nucleic acid probe labeled with the fluorescentdye and the target site in the nucleic acid are hybridized. Thus, theBCR gene, the ABL gene and the nucleus are respectively labeled withdifferent fluorescent dyes.

The image display apparatus 120 includes an image processing unit 121, astorage unit 122, a display unit 123, an input unit 124, and an imagingunit 200. The detailed configuration of the imaging unit 200 will bedescribed later with reference to FIG. 2. Note that the image displaydevice 120 may be configured to include the preprocessing unit 110.

The image processing unit 121 is configured by a CPU. The imageprocessing unit 121 may be configured by a CPU and a microcomputer. Theimage processing unit 121 performs various processes based on a programand data stored in the storage unit 122. The image processing unit 121is connected to the storage unit 122, the display unit 123, the inputunit 124, and the imaging unit 200, receives signals from each unit, andcontrols each unit. The storage unit 122 is configured by a RAM, a ROM,a hard disk, and the like. The display unit 123 is configured by adisplay. The input unit 124 includes a mouse and a keyboard.

The imaging unit 200 images a test substance contained in the sample 111based on a flow cytometry method, and generates a captured image.Specifically, the imaging unit 200 captures a sample 111 flowing throughthe flow cell and generates a captured image of the substance to beexamined for each cell. The test substance is the nucleus, the BCR gene,the ABL gene, and the whole cell as described above. For each cell, theimaging unit 200 generates fluorescence generated from a fluorescent dyethat stains the nucleus, fluorescence generated from a fluorescent dyethat stains the BCR gene, fluorescence generated from a fluorescent dyethat stains the ABL gene, and the light transmitted through the entirecell to generate a captured image. A captured image generated bycapturing light transmitted through the entire cell is a bright fieldimage.

The image processing unit 121 processes the captured image captured bythe imaging unit 200. More specifically, the image processing unit 121generates a display image including the region of the test substance sothat the position of the region of the test substance in the capturedimage differs from the position of the region of the test substance inthe display image by adding an additional image in which pixel values ofeach pixel are set so that the pixel values are unevenly distributed onat least a part of the captured image.

Note that the pixel value indicates a digital value assigned to eachpixel of the image. The pixel value of the first embodiment correspondsto the intensity of fluorescence generated from the fluorescent dye thatstains the test substance, or the intensity of the bright field lighttransmitted through the cell. In a captured image based on the nucleus,BCR gene and ABL gene, the pixel value is a value obtained by convertingthe brightness of the fluorescence generated from the fluorescent dyethat stains the nucleus, the BCR gene, and the ABL gene into digitalsignals. In the captured bright field image based on the cell, thebrightness of the light transmitted through the cell when the light isirradiated is converted into a digital signal.

FIG. 1B to FIG. 1G are schematic diagrams showing a procedure forgenerating a display image from a captured image with respect to thenucleus as a test substance.

When the captured image 11 shown in FIG. 1B is acquired by the imagingunit 200, as shown in FIG. 1C, the image processing unit 121 extractsthe nuclear region 21 in the captured image 11. Subsequently, the imageprocessing unit 121 sets the area 31 of the display image 61 so thatarea 21 is positioned at a predetermined position of the display image61 to be generated later. The predetermined position is, for example,substantially the center of the display image 61.

Subsequently, the image processing unit 121 removes the deletion image11 a on the outside of the area 31 in the captured image 11 from thecaptured image 11 as shown in FIG. 1E. In FIG. 1E, the deletion area 41is an area corresponding to the removed deletion image 11 a. An image 11b is generated by removing the deletion image 11 a from the capturedimage 11. Subsequently, as shown in FIG. 1F, the image processing unit121 generates an additional image 11 c corresponding to the additionalarea 51. The additional area 51 is an area located outside the capturedimage 11 in the area 31. At this time, the image processing unit 121sets the pixel value of each pixel of the additional image 11 c to beunevenly distributed among the pixels. Subsequently, the imageprocessing unit 121 combines the image 11 b shown in FIG. 1E and theadditional image 11 c shown in FIG. 1F to generate a display image 61shown in FIG. 1G.

When the display image 61 is generated in this way, the position of thenucleus region 21 in the captured image 11 is different from the nucleusregion 21 in the display image 61. That is, the region 21 of the nucleusin the image moves from a position other than the center tosubstantially the center. In the examples shown in FIG. 1B to FIG. 1G,the region 21 located at the lower left in the captured image 11 movessubstantially to the center in the display image 61.

The image processing unit 121 performs the procedure as shown in FIG. 1Bto FIG. 1G on not only the nucleus but also other test substances, thatis, the BCR gene, the ABL gene, and the cells, to create display images.Then, the image processing unit 121 displays display images based on thenucleus, the BCR gene, the ABL gene, and the cell on the display unit123.

The pixel value of each pixel is generally nonuniform in the regionother than the region of the test substance in a captured image, thatis, in the background region. When the display image is generated asdescribed above, the pixel values of each pixel of the additional imageare set so that the pixel values are unevenly distributed similar to thebackground area of the captured image. In this way, it is possible todisplay a natural display image in which the additional image is similarto the background area of the captured image. Hence, the operator canconcentrate on the region of the test substance without being distractedby the unnatural image, and can visually confirm the display imageefficiently.

As shown in FIG. 1D, the nucleus region 21 also is positionedsubstantially at the center in the region 31 of the display image 61. Asa result, the operator can confirm the nucleus at substantially thecenter of the display image 61, so that visual confirmation of thedisplay image 61 can proceed efficiently. Note that the region of thetest substance is not necessarily located at the center of the displayimage, and may be at the same position in the display image based oneach cell. In this case, the operator also can confirm the testsubstance at the same position of the display image 61, so that visualconfirmation of the display image can proceed efficiently.

Specific Configuration of the First Embodiment

As shown in FIG. 2, the imaging unit 200 includes a flow cell 210, lightsources 221 to 224, condenser lenses 231 to 234, dichroic mirrors 241and 242, a condenser lens 251, an optical unit 252, a condenser lens253, and a camera 254. A sample 111 is flowed through the flow channel211 of the flow cell 210.

The light sources 221 to 224 irradiate light on the sample 111 flowingthrough the flow cell 210. The light sources 221 to 224 are configuredby semiconductor laser light sources. The light beams emitted from thelight sources 221 to 224 are laser beams having wavelengths λ11 to λ14,respectively. The condensing lenses 231 to 234 collect light emittedfrom the light sources 221 to 224, respectively. The dichroic mirror 241transmits light of wavelength λ13 and reflects light of wavelength λ12.The dichroic mirror 242 transmits the light of the wavelengths λ12 andλ13 and reflects the light of the wavelength λ11. In this way, lighthaving wavelengths λ11 to λ14 is irradiated on the sample 111 flowingthrough the flow channel 211 of the flow cell 210.

When the sample 111 flowing through the flow cell 210 is irradiated withlight having wavelengths λ11 to λ13, fluorescence is generated from thefluorescent dyes staining the cells. That is, light of wavelengths λ11to λ13 emitted from the light sources 221 to 223 are excitation lightthat excite fluorescence from the fluorescent dye.

Specifically, when light of wavelength λ11 is irradiated on afluorescent dye that stains nuclei, fluorescence of wavelength λ21 isgiven off from this fluorescent dye. When the light with the wavelengthλ12 is irradiated on the fluorescent dye labeling the BCR gene, thefluorescence with the wavelength λ22 is given off from this fluorescentdye. When the light with the wavelength λ13 is irradiated on thefluorescent dye that labels the ABL gene, fluorescence with thewavelength λ23 is given off from this fluorescent dye. When the sample111 flowing through the flow cell 210 is irradiated with light having awavelength λ 14, this light transmits through the cell. The light havingthe wavelength λ14 that has passed through the cell is used forgenerating a bright field captured image. In the first embodiment, thewavelength λ21 is a wavelength band of blue light, the wavelength λ22 isa wavelength band of green light, and the wavelength λ23 is a wavelengthband of red light.

The condenser lens 251 collects the fluorescence of the wavelengths λ21to λ23 given off from the sample 111 flowing through the flow cell 210and the light of the wavelength λ14 transmitted through the sample 111flowing through the flow cell 210. The optical unit 252 has aconfiguration in which four dichroic mirrors are combined. The fourdichroic mirrors of the optical unit 252 reflect the fluorescence of thewavelengths λ21 to λ23 and the light of the wavelength λ14 at slightlydifferent angles from each other to separate them on the light receivingsurface of the camera 254. The condensing lens 253 collects thefluorescence of the wavelengths λ21 to λ23 and the light of thewavelength λ14.

The camera 254 is configured by a TDI (Time Delay Integration) camera.The camera 254 images the fluorescence of the wavelengths λ21 to λ23,and obtains three captured images which respectively correspond to thenucleus, the BCR gene, and the ABL gene. The camera 254 also images thelight having the wavelength λ14 and acquires a captured imagecorresponding to the bright field. The camera 254 successively imagesthe sample 111 flowing through the flow cell 210 and acquires fourcaptured images for each cell by separating the consecutively capturedimages from cell to cell. The four captured images acquired for one cellare imaged with the same timing and have the same shape and the samesize. The camera 254 transmits the acquired captured image to the imageprocessing unit 121 as an imaging signal. Note that the captured imageacquired by the camera 254 is a grayscale image.

In this way, when the sample 111 flowing through the flow cell 210 isimaged by the camera 254, a plurality of captured images based on thetest substance can be continuously acquired from one sample 111. Whenthe test substance is labeled with a fluorescent dye and thefluorescence given off from the fluorescent dye is captured by thecamera 254, the region and the position and the like of the testsubstance also can be visualized in the image via the fluorescence.Hence, the operator can confirm the state of the test substance smoothlyand clearly by referring to the display image. Note that the imagingunit 200 may be configured for imaging a test substance with amicroscope, instead of imaging the test substance based on the flowcytometry method.

A process using the preprocessing unit 110 and the image display device120 will be described with reference to the flowchart shown in FIG. 3.Each step of FIG. 3 will be described with reference to FIG. 4A to FIG.8 as appropriate.

In step S1, the preprocessing unit 110 performs preprocessing on thesample. As a result, the nucleus, the BCR gene, and the ABL gene in theleukocytes, which are the ells to be detected, are fluorescently labeledto prepare the sample 111. In step S2, the image processing unit 121controls the imaging unit 200 to obtain for each cell based on thesample 111, a captured image 11 based on the nucleus, a captured cell 12based on the BCR gene, a captured image 13 based on the ABL gene, and acaptured image 14 based on the bright field of the cell, as shown inFIG. 4A.

In step S3, the image processing unit 121 acquires regions 21 to 24 ofthe test substance from the captured images 11 to 14 as shown in FIG.4B. The region 21 is a region where the nucleus is distributed in thecaptured image 11. The region 22 is a region in which the BCR gene isdistributed in the captured image 12. The region 22 is a region in whichthe BCR gene is distributed in the captured image 12. The region 24 is aregion in which cell is distributed in the captured image 14.

The region of the test substance in step S3 is extracted, for example,as shown in FIG. 4C. When the captured image 11 is acquired as shown atthe left end of FIG. 4C, and the image processing unit 121 calculatesthe pixel value of the captured image 11 based on the pixel value ofeach pixel of the captured image 11, and creates graphs of pixel valuesand frequencies as shown in center of FIG. 4C. The frequency of thevertical axis indicates the number of pixels. In this graph, the imageprocessing unit 121 sets a threshold value of a pixel value as aboundary between the region of the test substance and the backgroundregion other than a test substance, for example, based on the Otsumethod. Then, the image processing unit 121 extracts a region wherepixels with pixel values larger than the threshold value are distributedas the region 21 of the test substance as indicated by the broken lineat the right end of FIG. 4C. Extraction of such a region of the testsubstance is similarly performed in the captured images 12 to 14.

In the above description, for convenience, the image processing unit 121generates a histogram as shown in FIG. 4C, but it is not necessary togenerate a histogram. The image processing unit 121 may acquire theregion of the test substance by performing calculation similar to thatin the case of generating the histogram.

In steps S4 and S5, the image processing unit 121 performs a clippingprocess and padding process. In steps S4 and S5, as shown in FIG. 5A,the image processing unit 121 sets regions 31 to 34 of the display imageon the captured images 11 to 14, respectively.

Specifically, the image processing unit 121 sets the area 31 so that thecenter of gravity of the nucleus region 21 in the captured image 11 ispositioned at the center. The region 31 is an area corresponding to theshape and size of the display image 61, and has a predetermined shapeand size. The shape of the region 31 in the first embodiment is asquare.

The image processing unit 121 sets the areas 32 to 34, which areentirely the same as the area 31 set for the captured image 11 of thenucleus, relative to the captured images 12 to 14, respectively. Thatis, the regions 32 to 34 have the same shape and the same size as thoseof the region 31. The position of the region 32 relative to the capturedimage 12, the position of the region 33 relative to the captured image13, and the position of the region 34 relative to the captured image 14are also the same as the position of the region 31 relative to thecaptured image 11. By setting the regions 31 to 34 in this way, thedisplay images 61 to 64 and 70 to be described later have constantshapes and constant sizes between the cells.

Subsequently, as shown in FIG. 5B, the image processing unit 121 sets,as the deletion area 41, the area outside the area 31 in the capturedimage 11 relative to the captured image 11, and sets the area on theouter side of the captured image 11 of the region 31 is defined as anadditional area 51. Similarly, the image processing unit 121 also setsthe deletion areas 42 to 44 for the captured images 12 to 14,respectively, and sets the additional areas 52 to 54.

In the clipping process of step S4, the image processing unit 121deletes the deletion image 11 a located within the deletion area 41 fromthe captured image 11, similar to the procedure described with referenceto FIGS. 1D and 1E. Then, in the padding process in step S5, the imageprocessing unit 121 adds an additional image 11 c to the added area 51relative to the captured image 11 from which the deletion image 11 a wasremoved as in the procedure described with reference to FIGS. 1E to 1G.The image processing unit 121 also corrects the color tone for the imagebased on the nucleus after the clipping process and the padding processso that the nucleus region 21 becomes blue. In this way, a display image61 related to the nucleus is generated, as shown in FIG. 5C.

Similarly, in the clipping process of step S4, the image processing unit121 deletes the image portions in the deletion areas 42 to 44 from thecaptured images 12 to 14, respectively. Then, in the padding process ofstep S5, the image processing unit 121 adds additional images to theadditional areas 52 to 54, respectively, for the captured images 12 to14 subjected to the padding process. The image processing unit 121 alsocorrects the color tone so that the region 22 of the BCR gene becomesgreen relative to the image based on the BCR gene for which the clippingprocess and the padding process have been completed. The imageprocessing unit 121 corrects the color tone so that the area 23 of theABL gene becomes red relative to the image based on the ABL gene forwhich the clipping process and the padding process have been completed.Note that the color tone is not corrected for the image based on thebright field where the clipping process and the padding process have notbeen completed. In this way, images for display 61 to 64 are generated,as shown in FIG. 5C.

In the padding process of step S5, similar to the case described withreference to FIG. 1F, the image processing unit 121 sets the pixel valueof each pixel of the additional image so as to be unevenly distributedamong the pixels. As a result, in any of the captured images 11 to 14,the additional image added in the padding process becomes an image thatfits the background area of the captured images 11 to 14. Therefore, inthe generated display images 61 to 64, the added additional imagebecomes an image familiar to the background area of the captured images11 to 14. Details of the padding process will be described later withreference to FIG. 9.

In the examples shown in FIGS. 4A to 5C, in the padding process, anadditional image is added to a captured image subjected to the clippingprocess, that is, a part of the captured image. For example, in thepadding process on the captured image 11, as shown in FIG. 6A, anadditional image 11 c is added to the image 11 b generated by theclipping process to generate a display image 61. However, an additionalimage may be added to the entire captured image without performing aclipping process on the captured image. Regarding the captured image inthis case, in the padding process, an additional image 11 c is added tothe captured image 11 acquired by the imaging unit 200 to generate adisplay image 61, as shown in FIG. 6B.

Thus, depending on the shape and size of the captured image and theposition of the substance to be examined, an additional image may beadded to the captured image that is not subjected to the clippingprocess to generate a display image in some cases. That is, in thepadding process, an additional image may be added to at least a part ofthe captured image.

Subsequently, in step S6, the image processing unit 121 generates adisplay image 70 by superimposing the display images 61 to 63 on eachother as shown in FIG. 7A. As described above, the display images 61 to63 are natural images in which the additional image is similar to thebackground area. Therefore, the background area before the additionimage is added and the area of the additional image also do not lookunnatural in the display image 70.

Note that in the overlaying method shown in FIG. 7A, the display images61 to 63 were superimposed without changing the shape and size. However,the method of superimposition is not limited to the method shown in FIG.7A if the shape and size of the generated display image 70 is the sameas shown in FIG. 7A and the region of the test substance is included inthe generated display image 70. For example, the display image 70 alsocan be generated by superposing the BCR gene region 22 of the displayimage 62 and the ABL gene region 23 of the display image 63 on thedisplay image 61.

Subsequently, in step S7, the image processing unit 121 analyzes thecells. Specifically, the image processing unit 121 detects abnormalcells by determining whether the BCR gene or the ABL gene is an abnormalcell that is translocated for each cell.

For example, in the display image 70 of FIG. 7A, when two greenluminescent spots and two red luminescent spots exist, the imageprocessing unit 121 determines that the BCR gene and the ABL gene arenot translocated, that is, the determination is negative. On the otherhand, as shown in the schematic view of FIG. 7B, when there are two redluminescent spots, one green luminescent spot, and one yellowluminescent spot in the display image 70, the image processing unit 121determines that translocation occurs in the BCR gene and the ABL gene,that is, the determination is positive for this cell. The reason theyellow bright spot occurs is that the green bright spot and the redbright spot are synthesized at the same position.

As shown in the schematic view of FIG. 7C, when there is one red brightspot, one green bright spot, and two yellow bright spots in the displayimage 70, the image processing unit 121 determines that translocationoccurs in the BCR gene and the ABL gene, that is, the determination ispositive for this cell. As shown in the schematic diagram of FIG. 7D,when there is one red bright spot, one green bright spot, and one yellowbright spot in the display image 70, the image processing unit 121determines that translocation occurs for the BCR gene and ABL gene, thatis, the determination is positive for this cell.

In step S7, the image processing unit 121 performs the determination ofabnormal cells for each cell as described above. In the determination ofabnormal cells, it is not always necessary to use the display image 70,inasmuch as the abnormal cell determination also can be made based onthe distribution of the BCR gene region 22 in the display image 62 andthe distribution of the ABL gene region 23 in the display image 63.

Subsequently, in step S8, the image processing unit 121 displays ascreen 300 for displaying the display images 61 to 64, and 70 on thedisplay unit 123 as shown in FIG. 8 according to the display instructionof the operator.

As shown in FIG. 8, the screen 300 includes regions 310, 320, 330, 340,and 350.

The date and time when the measurement was made and the sample ID of thesample which is the source of the information in screen 300 aredisplayed in region 310. The analysis result of step S7 is displayed inregion 320. The number and percentage of positive cells, the number andpercentage of negative cells, and the number and percentage of all cellsdetermined positive or negative are displayed in region 320. Comments onthe sample, comments on measurement and analysis and the like aredisplayed in region 330.

A plurality of display images 61 to 64, and 70 acquired in the imageprocessing step are displayed in region 340. In the example shown inFIG. 8, a list of display images 70 is displayed in the area 340. Notethat the display images 61 to 64 are also listed in the area 340 similarto the display image 70 by the use of a switching button or the like(not shown).

The area 340 also includes an operation unit 341 and buttons 342 to 344.The operator can scroll the display image in the area 340 and change thedisplay image to be displayed in the area 340 by operating the operationunit 341 via the input unit 124.

The operator can change the determination result of the selected cell byselecting the display image in the area 340 via the input unit 124 andpressing a button 342. The determination results that can be changedinclude not only positive and negative, but also “other” which indicatesthat proper determination can not be made because the staining state ofthe cell is poor. The operator selects an image for display in the area340 via the input unit 124 and presses the button 343 to restore thedetermination result on the selected cell to the determination resultbased on the analysis result in step S7. When the determination resultis changed, the result within the area 320 is automatically corrected.An enlarged image of the display image selected within the area 340 isdisplayed in the region 350.

When the operator visually confirms the display image displayed in thelist and determines that there is no problem in the analysis result, theoperator presses a button 344 via the input unit 124 to confirm theanalysis result.

As described above, the display image displayed on the screen 300 is anatural image in which the additional image is familiar to thebackground area. When visually confirming the image for display in thisway, the operator can concentrate on the region of the test substancewithout being distracted by an unnatural image and efficiently performvisual confirmation of the image for display. A plurality of displayimages generated from the same sample 111 also are listed and displayedon the screen 300. In this way, the operator can easily compare andcontrast the images for display based on the same sample 111. Thedisplay image displayed on the screen 300 also is set to have a fixedshape and a fixed size between the cells. In this way, it is possible toenhance work efficiency when observing the state of the test substancevisually.

The nucleus region 21 also is positioned substantially at the center ofthe image for display for all cells. In this way, the operator canalways check the substance to be examined at substantially the center ofthe display image, so that the visual confirmation of the display imagecan be efficiently advanced. Note that the nucleus region 21 does notnecessarily have to be located at the center of the image for displayand may be at the same position in the image for display of each cell.The operator also can efficiently conduct visual confirmation since theoperator can confirm the test substance at the same position in thiscase.

A display image 62 based on the BCR gene and a display image 63 based onthe ABL gene also are displayed on the screen 300. In this way, theoperator can confirm the translocation of these genes, for example, withreference to the display images 62 and 63, and diagnosis based on thesegenes is facilitated smoothly and efficiently. A display image 70 inwhich a display image 62 based on the BCR gene and a display image 63based on the ABL gene are superimposed also is displayed on the screen300. In this way, the operator can easily confirm the distribution stateof the BCR gene and the ABL gene with reference to the display image 70.Therefore, for example, it can be easily confirmed whether translocationhas occurred in these genes, and the diagnosis can proceed smoothly.

The display image 70 displayed on the screen 300 also is generated byoverlapping the display image 61 based on the nucleus and the displayimages 62 and 63 based on the genes. In this way the operator canascertain how the gene is distributed in the nucleus. For example, iflight generated from a fluorescent dye that labels a gene is distributedoutside the nucleus, it can be determined that the fluorescent labelingof the gene was not performed properly.

First Embodiment Padding Process

A padding process according to the first embodiment will be describedwith reference to FIG. 9. Note that since the padding process for thecaptured images 11 to 14 that have been subjected to the clippingprocess is the same in each instance, only the case of the capturedimage 11 based on the nucleus will be described in the followingdescription for convenience. Hereinafter, each step of FIG. 9 will bedescribed with reference to FIGS. 10A to 11A as appropriate.

As shown in FIG. 10A, in the clipping process performed before thepadding process, the deleted image 11 a is removed from the capturedimage 11, so that the image 11 b is generated as described above. Whenthe padding process is started, in step S11, the image processing unit121 reads the pixel value of each pixel in the background region 91other than the nucleus area 21 in the image 11 b. The background region91 is a hatched area in FIG. 10B.

Here, in order to recognize the background region 91 of the image 11 b,the image processing unit 121 uses a mask image 91 a based on the image11 b and the nucleus region 21 as shown in FIG. 10B. The mask image 91 ais an image having the same shape and size as the image 11 b and pixelsin a region other than the nucleus region 21 are set to black. In stepS11, the image processing unit 121 identifies the portion of the image11 b at the position of the black pixels of the mask image 91 a as thebackground region 91 of the image 11 b by applying the mask image 91 ato the image 11 b. Then, the image processing unit 121 reads the pixelvalue of each pixel in the background region 91 of the image 11 b.

Note that although the background area to be processed in step S11 isthe background region 91 other than the region 21 of the image 11 b, thepresent invention is not limited to this arrangement inasmuch as anotherbackground region 92 other than the region 21 of the captured image 11also may be specified, as shown in FIG. 10C. In this case, the imageprocessing unit 121 identifies the background region 92 of the capturedimage 11 by applying the mask image 92 a to the captured image 11. Thebackground region to be targeted in step S11 also may be a partial areain the vicinity of the background region 91 to which the additionalimage 11 c is added.

Subsequently, in step S12, the image processing unit 121 acquiresbackground information based on the pixel value of the background region91 read in step S11. In the padding process according to the firstembodiment, the background information is an average value of the pixelvalue of each pixel in the background region 91 of the image 11 b, thatis, an average pixel value.

Subsequently, in step S13, the image processing unit 121 adds a randomnumber of positive or negative polarity for each pixel to the averagepixel value, thereby setting the pixel value of each pixel of theadditional image 11 c. At this time, the image processing unit 121 setsthe pixel value of each pixel of the additional image 11 c by changingthe pixel value for each pixel relative to the average pixel value.

As shown in FIG. 11A, in step S13, a random number generated in a rangefrom −Δw to +Δw is added to the average pixel value. In this case, arange of the random number set in advance to be small is stored in thestorage unit 122 so that the value obtained by adding the random numberto the average pixel value falls between the expected minimum pixelvalue and the expected maximum pixel value. The expected minimum pixelvalue is the minimum pixel value that is statistically expected in thebackground region 91, and the expected maximum pixel value is themaximum pixel value that is statistically expected in the backgroundregion 91.

Then, in step S14, the image processing unit 121 adds the additionalimage 11 c in which the pixel value is set in step S13 to the image 11 bto generate the display image 61.

In the histogram shown in FIG. 11B, the background region 91 in theimage 11 b is identified by applying the corresponding mask image 91 ain FIG. 11B to the image 11 b in FIG. 11B, and the identified backgroundregion 91 on the basis of the pixel value of each pixel. Similarly, thehistogram shown in FIG. 11C is created based on the pixel value of eachpixel of the identified background region 91 when the background region91 in the image 11 b is identified by applying the corresponding maskimage 91 a in FIG. 11C to the image 11 b in FIG. 11C. The pixel value ofeach pixel of the image 11 b in FIGS. 11B and 11C are represented by 256gradations from 0 to 255. The horizontal axis and the vertical axis ofthe histogram of FIGS. 11B and 11C respectively indicate the pixel valueand the frequency. In any of the histograms of FIGS. 11B and 11C, thepixel values of the background region 91 are distributed in a peakedshape at the low value.

According to the padding process of the first embodiment, a randomnumber generated in the range from −Δw to +Δw is added to the averagepixel value acquired from the background region 91 as shown in FIG. 11A.Therefore, the pixel value of the additional image 11 c can be setwithin the pixel value range close to the average pixel value of thebackground region 91. Hence, the difference in pixel value between thebackground region 91 and the additional image 11 c of the image 11 b canbe suppressed, and a natural image can be generated in which theadditional image 11 c is similar to the background region 91 of theimage 11 b.

As described above, the pixel value of each pixel of the additionalimage 11 c is set by adding a random number of positive or negativepolarity for each pixel to the average pixel value. By such a simpleprocess, the noise component of the pixel value occurring in thebackground region 91 can be expressed in the additional image 11 c. Thepixel value of each pixel of the additional image 11 c also is set sothat the pixel value changes on the basis of the random number for eachpixel relative to the average pixel value. In this way, the noisecomponent of the pixel value occurring in the background region 91 canbe expressed in the additional image 11 c, and a more natural displayimage 61 can be generated.

Such a padding process is performed on the captured image 11 obtainedfor each cell. In this way, the additional images 11 c set according tothe captured image 11 are mutually different from each other accordingto the background region 91 of each captured image 11. Therefore, sincethe display image 61 for each cell is a natural image similar to theadditional image 11 c, the operator can concentrate on the region of thetest substance without being distracted by unnatural images in visualconfirmation.

FIG. 12A is a diagram showing the display image 61 actually generatedfrom the image 11 b shown in FIGS. 11B and 11C by the padding process ofthe first embodiment. In this case, it can be seen that the noisecomponent of the pixel values occurring in the background region isexpressed in the additional image. On the other hand, FIG. 12B is adiagram showing a display image actually generated from the image 11 bshown in FIGS. 11B and 11C by the padding process of a comparativeexample. In the padding process of the comparative example, the regioncorresponding to the additional image is filled with the average pixelvalue of the background region 91. Comparing FIG. 12A and FIG. 12B, thedisplay image 61 generated by the padding process of the firstembodiment is a natural image in which the additional image 11 c issimilar to the image 11 b of the background region 91.

Modification Example of Padding Process of First Embodiment

As shown in FIG. 13A, in the modification example of the padding processof the first embodiment, steps S15 and S16 are added instead of step S12as compared with the padding process of the first embodiment shown inFIG. 9. Steps different from the padding process of the first embodimentwill be described below.

In step S15, the image processing unit 121 acquires the maximum pixelvalue and the minimum pixel value of the pixels in the background region91 of the image 11 b in addition to the average pixel value similar tothe padding process of the embodiment as the background information.Then, in step S16, the image processing unit 121 sets the range ofrandom numbers so that the value obtained by adding the random numbervalue to the average pixel value is included between the maximum pixelvalue and the minimum pixel value as shown in FIG. 13B. In step S13,similarly to the padding process of the first embodiment, the imageprocessing unit 121 sets the pixel value of each pixel of the additionalimage 11 c by adding a random number of positive or negative polarityfor each pixel to the average pixel value.

When the pixel value of each pixel of the additional image 11 c is setin this way, the noise component expressed in the additional image 11 cbecomes less conspicuous to the background region 91 because the pixelvalue of the additional image 11 c always fits within the pixel valuechange range of the background region 91 of the image 11 b.

Second Embodiment

The second embodiment differs from the first embodiment only in thepadding process. As shown in FIG. 14A, the padding process of the secondembodiment is different from the padding process of the first embodimentshown in FIG. 9 in that step S21 is added instead of step S12, and stepS22 is added instead of step S13. Steps different from the paddingprocess of the first embodiment will be described below.

In step S21, the image processing unit 121 acquires the maximum pixelvalue and the minimum pixel value of the pixels in the background region91 of the image 11 b as background information. Then, in step S22, theimage processing unit 121 sets the pixel value of each pixel of theadditional image 11 c with a random number that changes between themaximum pixel value and the minimum pixel value as shown in FIG. 14B.

When the pixel value of each pixel of the additional image 11 c is setin this way, the noise component expressed in the additional image 11 cbecomes less conspicuous to the background region 91 because the pixelvalue of the additional image 11 c always fits within the pixel valuechange range of the background region 91 of the image 11. In this case,however, since the pixel value of the additional image 11 c is evenlydistributed between the maximum pixel value and the minimum pixel value,as shown in the histograms of FIGS. 11B and 11C, the distribution of thepixel values of the background region 91 is somewhat different.Therefore, as in the padding process of the first embodiment, it ispreferable that a random number is added with the average pixel value asthe center.

Steps S11 and S21 are omitted, and in step S22, the expected maximumpixel value and expected minimum pixel value previously stored in thestorage unit 122 also may be used instead of the maximum pixel value andthe minimum pixel value acquired from the background region 91 of theimage 11 b. In this case, although there is a possibility that the pixelvalue set by the random number may be smaller than the actual minimumpixel value or may be larger than the actual maximum pixel value, thenoise component expressed in the additional image 11 c becomes lessconspicuous relative to the background region 91 of the captured image11.

Modification Example of Padding Process of the Second Embodiment

In the modification example of the padding process of the secondembodiment, steps S11 and S21 shown in FIG. 15A are omitted and step S23is added instead of the step S22 as shown in FIG. 15A as compared withthe padding process of the second embodiment shown in FIG. 14A. Stepsdifferent from the padding processing of the second embodiment will bedescribed below.

In step S23, the image processing unit 121 sets the pixel value of eachpixel of the additional image 11 c by adding a random number of positiveor negative polarity to each pixel relative to the expected averagepixel value, as shown in FIG. 15B. The expected average pixel value is astatistically predicted pixel value as an average value of each pixel inthe background region 91 of the image 11 b. The expected average pixelvalue is stored in the storage unit 122 in advance. Also in this case,the range of the random numbers set to be small in advance is stored inthe storage unit 122 so that the value of the random number added to theexpected average pixel value falls between the expected maximum pixelvalue and the expected minimum pixel value.

When the pixel value of each pixel of the additional image 11 c is setin this way, the pixel values of the additional image 11 c can be setwithin the pixel value range near to the average pixel value similar tothe background region 91. Therefore, it is possible to suppress thedifference in pixel value between the background region 91 and theadditional image 11 c of the image 11 b, and to display a natural imagein which the additional image 11 c is similar to the background region91 of the image 11 b. In this case, it also is not necessary to acquirebackground information, so the processing steps can be simplified.However, in this case, the average pixel value obtained from thebackground region 91 of the image 11 b is preferably used when settingthe pixel value of the additional image 11 c, since the expected averagepixel value may be greatly different from the average pixel value of theactual background region 91.

Third Embodiment

The third embodiment differs from the first embodiment only in thepadding process. As shown in FIG. 16A, the padding process according tothe third embodiment is different from the padding process of the firstembodiment shown in FIG. 9 in that step S31 is added following step S14.Steps different from the padding process of the first embodiment will bedescribed below.

In step S14, an additional image 11 c is added to the image 11 b togenerate a display image 61. In step S31, the image processing unit 121performs a smoothing process on the display image 61 to suppress pixelvalue change. As shown in FIG. 16B, the smoothing process applicationregion is a region obtained by removing the nucleus region 21 of thetest substance from the entire region of the display image 61. Note thatthe smoothing process application region may be set to include at leastthe vicinity of the boundary between the additional image 11 c and thebackground region 91 of the captured image 11.

As shown in FIG. 16C, when the pixel value of the target pixel is Vx andthe pixel values of the eight pixels around the target pixel are V1 toV8, the image processing unit 121 calculates Vx=(V1+V2+ . . . +V8)/8 inthe smoothing process. In step S31, the image processing unit 121 shiftsthe target pixel sequentially in the smoothing process applicationregion and performs the above calculation, then sets the pixel value ofthe target pixel to Vx. When calculation of pixel values is performedonce for all the pixels in the smoothing process application region, thesmoothing process is terminated.

As shown in FIGS. 16D and 16E, when the target pixel is located at theend of the smoothing process application region, the pixel value of thepixel outside the smoothing process application region is designated thepixel value of the pixel at the symmetric position inside the smoothingprocess application region. Therefore, the pixel value Vx of the targetpixel is acquired by calculation of Vx=(2 V 2+4 V 3+2 V 5)/8 in the caseof FIG. 16D, and acquired by Vx=(2 V 1+2V2+2V3+V 4+V 5)/8 in the case ofFIG. 16E. As shown in FIG. 16F, the calculation of pixel value Vx of thetarget pixel can be obtained by calculation similar to FIG. 16C withoutthe relationship between the additional image 11 c and image 11 b aslong as the pixel value Vx of the target pixel is within the smoothingprocess application region.

FIG. 17A is a diagram showing a display image 61 in which the smoothingprocess is actually performed by the padding process of the thirdembodiment. The display image 61 in FIG. 17A is generated by performingthe smoothing process described in step S31 of FIG. 16A on the displayimage 61 shown in FIG. 12A. When referencing a region other than thenucleus region 21 of the display image 61, although the pixel values ofthe adjacent pixels are opened in the case of FIG. 12A, the pixel valuesof the adjacent pixels are brought closer in the case of FIG. 17A toobtain a pattern of pixel values that is smooth overall in a regionother than the region 21 of the nucleus.

According to the padding process of the third embodiment, since thesmoothing process is executed on at least the pixels in the vicinity ofthe boundary between the additional image 11 c and the background region91 of the image 11 b, the continuity if improved between the additionalimage 11 c and the background region 91 of the image 11 b, thusgenerating a more natural display image 61. Since the smoothing processaccording to the third embodiment is performed on the entire regionother than the nucleus region 21, it also is possible to suppress asense of incompatibility in the entire background portion.

In the smoothing process according to the third embodiment, the pixelvalue Vx of the target pixel also may be set by performing thecalculation of Vx=(V 1+V 2+V 3+V 4)/4 (4) based on the pixel values ofthe four surrounding pixels of the target pixel, as shown in FIG. 17B,as shown in FIG. 17B. As shown in FIG. 17C, the pixel value Vx of thetarget pixel also may be set by performing the calculation of Vx=(V1+V2+. . . +V24)/24 based on the pixel values of the 24 pixels around thetarget pixel. In this way, the number of surrounding pixels used forsetting the pixel value Vx of the target pixel is not limited to theeight pixels in FIG. 16C. In the smoothing process, the number of timesto calculate the pixel values for all the pixels in the applicationregion of the smoothing process is not limited to once inasmuch as thecalculation may be performed a plurality of times.

Fourth Embodiment

The fourth embodiment differs from the first embodiment only in thepadding process. As shown in FIG. 18A, the padding process of the fourthembodiment is different from the padding process of the first embodimentshown in FIG. 9 in that step S41 is added instead of step S12, and stepS42 is added instead of step S13. Steps different from the paddingprocess of the first embodiment will be described below.

In step S41, the image processing unit 121 acquires the average pixelvalue, the maximum pixel value, the minimum pixel value, and thestandard deviation of the pixels of the image 11 b in the backgroundregion 91 as background information. Then, in step S42, the imageprocessing unit 121 sets the pixel value of each pixel of the additionalimage 11 c based on the background information, so that the pixel valuesof the additional image 11 c are distributed with the same tendency asthe frequency distribution of the pixel values of the background region91.

FIG. 18B is a diagram showing the display image 61 actually generatedfrom the image 11 b shown in FIG. 11B and FIG. 11C by the paddingprocessing of the fourth embodiment. In the case of FIG. 18B, it can beseen that the pixel value of each pixel expressed in the additionalimage 11 c is closer to the noise component of the pixel value generatedin the background region 91 of the image 11 b as compared with the firstembodiment shown in FIG. 12A. As described above, according to thepadding process of the fourth embodiment, a more natural display image61 can be generated since the noise component can be expressed in theadditional image 11 c with a pixel value distribution similar to thenoise component occurring in the background area 91.

Here, the arithmetic expression used in step S42 will be described indetail.

The frequency distribution of the pixel values of the background region91 has the same distribution as the Gaussian distribution. In step S42,the pixel value of each pixel of the additional image 11 c is set basedon the function defining the Gaussian distribution, the average pixelvalue of the background region, the maximum pixel value, the minimumpixel value, the standard deviation of the pixel value, and a randomnumber equally distributed in a predetermined range. Specifically, thepixel value of each pixel of the additional image 11 c is set accordingto the following expression (1).Z=F ⁻¹(F(α)+U·(F(β)−F(α))·σ+μ  (1)

Where α and β in expression (1) are given by the following expressions(2) and (3).α=(a−μ)/σ  (2)β=(b−μ)/σ  (3)

The parameters of the expressions (1) to (3) are as follows.

Z: Pixel value of each pixel.

F: Cumulative distribution function of standard Gaussian distribution(μ=0, σ=1).

F⁻¹: Inverse function of cumulative distribution function F.

U: Random number occurring equally in the range of 0 to 1.

μ: Average pixel value of background area.

σ: Standard deviation of the pixel value of the background region.

a: Minimum pixel value of the background region.

b: maximum pixel value of the background area.

The cumulative distribution function F (t) is given by the followingexpression (4).

$\begin{matrix}{{F(t)} = {\frac{1}{2}\left( {1 + {{erf}\left( \frac{t}{\sqrt{2}} \right)}} \right)}} & (4)\end{matrix}$

The derivation process of expression (1) is described below.

FIG. 19A shows the probability density function f(x) of the standardGaussian distribution (μ=0, σ=1). The probability density function f(x)is given by the following equation (5).

$\begin{matrix}{{f(x)} = {\frac{1}{\sqrt{2\pi}}e^{\frac{- x^{2}}{2}}}} & (5)\end{matrix}$

FIG. 19B shows the probability density function t(x) of the restrictedGaussian distribution in which the standard Gaussian distribution islimited to the range of values α to β on the horizontal axis. When thevalue on the horizontal axis is outside the range of values α to β, thevalue of the probability density function t(x) is zero. Here, theprobability density function t(x) is given by the following expression(6).t(x)=f(x)/(F(β)−F(α))  (6)

FIG. 20A shows the cumulative distribution function T(x) of therestricted Gaussian distribution (μ=0, σ=1, α≤x≤β) shown in FIG. 19B.The cumulative distribution function T(x) is given by the followingexpression (7).T(x)=(F(x)−F(α))/(F(β)−F(α))  (7)

FIG. 20B shows the inverse function T(x)⁻¹(x) of the cumulativedistribution function T(x) shown in the expression (7). Inverse functionT⁻¹(x) is given by the following expression (8).T ⁻¹(x)=F ⁻¹(F(α)+x·(F(β)−F(α)))  (8)

Here, according to the inverse transformation method, when the variablex is a random number uniformly occurring in the range of 0 to 1, T⁻¹(x)is randomly distributed in the frequency distribution of the restrictedGaussian distribution shown in FIG. 19B. Therefore, values can begenerated to be distributed in the frequency distribution shown in FIG.21A by multiplying the value of T⁻¹ by the standard deviation σ andadding the average pixel value μ to derive the following equation (9).Z=T ⁻¹(U)·σ+μ  (9)

Here, U is a random number equally occurring in the range of 0 to 1similar to the variable x.

Expression (1) above is obtained by substituting expression (8) intoexpression (9). Therefore, after applying the standard deviation of theaverage pixel value, the maximum pixel value, the minimum pixel value,and the pixel value acquired from the background region 91 to expression(1), the pixel values of the additional image 11 c are distributed witha tendency similar to the frequency distribution of the backgroundregion 91 by substituting the random number U for each pixel of theadditional image 11 c, and setting the pixel value.

Note that in the case where an additional region 51 is set as shown inFIG. 21B, the additional region 51 may be divided into a region R1 and aregion R2, and pixel values for each pixel may be individually set forthe regions R1 and R2, or the pixel value for each pixel may be set forthe entire additional region 51.

Although the average pixel value, the maximum pixel value, the minimumpixel value, and the standard deviation are acquired from the backgroundregion 91 of the image 11 b in step S41, alternatively the statisticallyexpected average pixel value, the maximum pixel value, the minimum pixelvalue, and the standard deviation also may be read in advance fromstorage unit 122 similar to each value of the background region 91 ofthe image 11 b. In this case, on the basis of each read value, the pixelvalue of each pixel of the additional image 11 c is set in step S42.

Fifth Embodiment

The fifth embodiment differs from the fourth embodiment only in thepadding process. As shown in FIG. 22A, the padding process according tothe fifth embodiment differs from the padding process of the fourthembodiment shown in FIG. 18A in that step S51 is added to the latterstage of step S14. Hereinafter, steps different from the paddingprocessing of the fourth embodiment will be described.

In step S14, an additional image 11 c is added to the image 11 b togenerate a display image 61. In step S51, the image processing unit 121performs a smoothing process on the display image 61 to suppress thepixel value change. The smoothing process of the fifth embodiment isperformed in the same way as the smoothing process of the thirdembodiment.

FIG. 22B is a diagram showing the display image 61 actually subjected tothe smoothing processing by the padding processing of the fifthembodiment. The display image 61 in FIG. 22B is an image generated byperforming the smoothing processing in step S51 on the display image 61shown in FIG. 18B. When referencing a region other than the nucleusregion 21 of the display image 61, although the pixel values of adjacentpixels are opened as in the case of FIG. 18B, the pixel values of thepixels are brought closer to each other in the case of FIG. 22B, and apattern of pixel values that is smooth overall is obtained in a regionother than the region 21 of the nucleus.

According to the padding process of the fifth embodiment, similar to thepadding process of the third embodiment, the continuity between thebackground area 91 and the additional image 11 c of the captured image11 is improved so that a more natural display image 61 can be generated.Since the smoothing process according to the fifth embodiment is alsoperformed on the entire region other than the nucleus region 21, it ispossible to suppress a sense of incompatibility in the entire backgroundportion. However, in the padding process of the fifth embodiment, asshown in FIG. 22B, the background region 91 of the image 11 b changesfrom its original state. Therefore, when it is determined that theoriginal image is preferred, it is preferable to generate the displayimage 61 by the padding processing of the fourth embodiment.

Sixth Embodiment

The sixth embodiment differs from the first embodiment only in thepadding process. As shown in FIG. 23A, the padding process of the sixthembodiment is different from the padding process of the first embodimentshown in FIG. 9 in that step S61 is added instead of step S13, and stepS62 is added in the latter stage of step S14. Steps different from thepadding process of the first embodiment will be described below.

In step S61, the image processing unit 121 sets the pixel value of eachpixel of the additional image 11 c with the average pixel value acquiredin step S12. In this way, the pixel value of all the pixels of theadditional image 11 c becomes the average pixel value. In step S14, theadditional image 11 c is added to the image 11 b to generate a displayimage 61. Then, in step S62, the image processing unit 121 performs asmoothing process for suppressing pixel value change on the displayimage 61. The smoothing process of the sixth embodiment is performed inthe same manner as the smoothing process of the third embodiment.

FIG. 23B is a diagram showing the display image 61 actually subjected tothe smoothing processing by the padding processing of the sixthembodiment. The display image 61 of FIG. 23B is an image generated byperforming the smoothing process of step S62 on the image of thecomparative example shown in FIG. 12B. Referring to FIG. 23B, pixelvalues of adjacent pixels are set smoothly in the vicinity of theboundary between the area of the additional image 11 c and the areaother than the additional image 11 c. That is, according to the paddingprocess of the sixth embodiment, it is understood that an image 61 fornatural display is generated as compared with the image of thecomparative example of FIG. 12B.

According to the padding process of the sixth embodiment, similar to thepadding process of the fifth embodiment, the continuity between thebackground region 91 and the additional image 11 c of the captured image11 is improved so that a more natural display image 61 can be generated.Since the smoothing process according to the sixth embodiment is alsoexecuted for the entire region other than the nucleus region 21, a senseof incompatibility in the entire background portion can be suppressed.

What is claimed is:
 1. An image display apparatus for imaging anddisplaying a test substance contained in a sample, the apparatuscomprising: an imaging unit configured to capture an image of the testsubstance; an image processing unit configured to generate a displayimage including a region of the test substance by adding an additionalimage in which pixel values are unevenly distributed to at least a partof the captured image so that the region of the test substance ispositioned substantially at a center of the display image; and a displayunit configured to display the display image.
 2. The image displayapparatus according to claim 1, wherein the image processing unitgenerates the display image so that a position of the region of the testsubstance in the captured image and a position of the region of the testsubstance in the display image are different.
 3. The image displayapparatus according to claim 1, wherein the display unit displays a listof a plurality of display images generated from a same sample.
 4. Theimage display apparatus according to claim 3, wherein the imaging unitcaptures images of a plurality of same type of test substances; theimage processing unit generates the display images so that positions ofthe region of the test substance in the display images are mutually samefor a plurality of captured images based on the plurality of the sametype of test substances.
 5. The image display apparatus according toclaim 4, wherein the image processing unit generates, for the pluralityof captured images, the display images by adding mutually differentadditional images corresponding to a background region other than theregion of the test substance to at least a part of the captured image.6. The image display apparatus according to claim 3, wherein the imageprocessing unit sets the display image to a fixed shape and a fixedsize.
 7. The image display apparatus according to claim 1, wherein theimage processing unit acquires an average pixel value of a backgroundregion other than the region of the test substance from the capturedimage and calculates the pixel value of each pixel of the additionalimage on the basis of the acquired average pixel value.
 8. The imagedisplay apparatus according to claim 7, wherein the image processingunit sets the pixel value of each pixel of the additional image bychanging the pixel value for each pixel relative to the average pixelvalue.
 9. The image processing apparatus according to claim 8, whereinthe image processing unit sets the pixel value of each pixel of theadditional image by adding a random number of positive or negativepolarity to each of the average pixel value of each pixel.
 10. The imagedisplay apparatus according to claim 7, wherein the image processingunit sets the pixel value of each pixel of the additional image byacquiring a maximum pixel value and a minimum pixel value of thebackground region, and adding a random number of positive or negativepolarity for each pixel relative to the average pixel value so that thepixel value of each pixel of the additional image is included between atleast the maximum pixel value and minimum pixel value.
 11. The imagedisplay apparatus according to claim 1, wherein the image processingunit acquires an average pixel value similar to an average pixel valueof a background region other than the region of the test substance inthe captured image, and sets the pixel value of each pixel of theadditional image based on the acquired average pixel value.
 12. Theimage display apparatus according to claim 11, wherein the imageprocessing unit sets the pixel value of each pixel of the additionalimage by acquiring a maximum pixel value and a minimum pixel value thatare the same as the maximum pixel value and the minimum pixel value ofthe background region, respectively, and adds the pixel value of eachpixel relative to the average pixel value so that the pixel value ofeach pixel of the additional image is included between at least theacquired maximum pixel value and minimum pixel value.
 13. The imagedisplay apparatus according to claim 1, wherein the image processingunit sets the pixel value of each pixel of the additional image so thatthe pixel values of the additional image are distributed with the sametendency as the frequency distribution of the pixel values of thebackground region other than the region of the test substance in thecaptured image.
 14. The image display apparatus according to claim 13,wherein the image processing unit sets the pixel value of each pixel ofthe additional image by setting a function that defines the relationshipbetween the random number and the pixel value based on the frequencydistribution of the pixel values of the background region, and appliesthe random number to the set function.
 15. The image display apparatusaccording to claim 14, wherein the image processing unit sets thefunction that defines the relationship between the random number and thepixel value by acquiring the variance of the frequency distribution ofthe pixel values of the background region, multiplying the inversefunction of the function representing the Gaussian distribution by theacquired variance, and adding the average pixel value of the backgroundregion.
 16. The image display apparatus according to claim 13, whereinthe image processing unit sets the pixel value of each pixel of theadditional image by setting a function that defines the relationshipbetween the random number and the pixel value based on the frequencydistribution of the pixel values of the background region, and appliesthe random number to the set function.
 17. The image display apparatusaccording to claim 16, wherein the image processing unit sets thefunction that defines the relationship between the random number and thepixel value by acquiring the variance of the frequency distribution ofthe pixel values of the background region, multiplying the inversefunction of the function representing the Gaussian distribution by theacquired variance, and adding the average pixel value of the backgroundregion.
 18. The image display apparatus according to claim 1, whereinthe image processing unit sets the pixel value of each pixel of theadditional image by acquiring a maximum pixel value and a minimum pixelvalue of a background region other than a region of the test substancein the captured image, and using a random number that changes in a rangebetween the acquired maximum pixel value and a minimum pixel value ofthe background region.
 19. The image display apparatus according toclaim 1, wherein the image processing unit sets the pixel value of eachpixel of the additional image by acquiring a maximum pixel value and aminimum pixel value respectively similar to the maximum pixel value andminimum pixel value of a background region other than a region of thetest substance in the captured image, and using a random number thatchanges in a range between the acquired maximum pixel value and aminimum pixel value of the background region.
 20. The image processingapparatus according to claim 1, wherein the image processing unitexecutes a smoothing process for suppressing a pixel value change for atleast pixels in a vicinity of a boundary between the additional imageand a background region of the captured image.
 21. An image displayapparatus for imaging and displaying a test substance contained in asample, the apparatus comprising: an imaging unit configured to capturean image the test substance; an image processing unit configured togenerate a display image including a region of the test substance byadding an additional image in which pixel values are unevenlydistributed to at least a part of the captured image so that the regionof the test substance is positioned substantially at a center of thedisplay image; and a display unit configured to display a list of aplurality of display images generated by the image processing unit froma same sample.
 22. An image display apparatus for imaging and displayinga test substance contained in a sample, the apparatus comprising: animaging unit configured to capture an image the test substance; an imageprocessing unit configured to generate a display image including aregion of the test substance from the captured image; a display unitconfigured to display the display image; wherein the image processingunit is further configured to: acquire a plurality of statistical valuesrelating to pixel values of a background region other than the region ofthe test substance from the captured image; create an additional imagein which pixel values are set to be unevenly distributed based on thestatistical values; and generate the display image by adding theadditional image to at least a part of the captured image so that theregion of the test substance is positioned substantially at a center ofthe display image.
 23. An image display method for imaging anddisplaying a test substance contained in a sample, the methodcomprising: capturing an image of a test substance; adding an additionalimage in which pixel values are unevenly distributed to at least a partof the captured image, and generating a display image so that a positionof a region of the test substance in the captured image is positionedsubstantially at a center of the display image; and displaying thegenerated display image.
 24. An image processing method for generating adisplay image including a region of a test substance from a capturedimage obtained by imaging a test substance; the method comprising:adding an additional image in which pixel values are unevenlydistributed to at least a part of the captured image, and generating adisplay image so that a position of the region of the test substance ispositioned substantially at a center of the display image.
 25. An imagedisplay apparatus for imaging and displaying a test substance containedin a sample, the apparatus comprising: an imaging unit configured tocapture an image of the test substance; an image processing unitconfigured to add an additional image in which pixel values are unevenlydistributed to at least a part of the captured image, and to generate adisplay image including a region of the test substance; and a displayunit configured to display the display image, wherein the imageprocessing unit is further configured to: acquire an average pixel valueof a background region other than the region of the test substance fromthe captured image; and calculate the pixel values of at least somepixels of the additional image based on the acquired average pixelvalue.
 26. An image display apparatus for imaging and displaying a testsubstance contained in a sample, the apparatus comprising: an imagingunit configured to capture an image of the test substance; an imageprocessing unit configured to add an additional image in which pixelvalues are unevenly distributed to at least a part of the capturedimage, and to generate a display image including a region of the testsubstance; and a display unit configured to display the display image,wherein the image processing unit is further configured to: acquire anaverage pixel value similar to an average pixel value of a backgroundregion other than the region of the test substance in the capturedimage; and set the pixel values of at least some pixels of theadditional image based on the acquired average pixel value.
 27. An imagedisplay apparatus for imaging and displaying a test substance containedin a sample, the apparatus comprising: an imaging unit configured tocapture an image of the test substance; an image processing unitconfigured to add an additional image in which pixel values are unevenlydistributed to at least a part of the captured image, and to generate adisplay image including a region of the test substance; and a displayunit configured to display the display image, wherein the imageprocessing unit is further configured to set the pixel value of at leastsome pixels of the additional image so that the pixel values of theadditional image are distributed with the same tendency as the frequencydistribution of the pixel values of the background region other than theregion of the test substance in the captured image.
 28. An image displayapparatus for imaging and displaying a test substance contained in asample, the apparatus comprising: an imaging unit configured to capturean image of the test substance; an image processing unit configured toadd an additional image in which pixel values are unevenly distributedon at least a part of the captured image, and to generate a displayimage including a region of the test substance; and a display unitconfigured to display the display image, wherein the image processingunit is further configured to execute a smoothing process forsuppressing a pixel value change for at least pixels in a vicinity of aboundary between the additional image and a background region of thecaptured image.